Asians were known to have a relatively lower incidence of venous thromboembolism (VTE), and there is insufficient evidence to suggest a specific D-dimer threshold level for screening VTE in patients with acute stroke.
We prospectively enrolled patients with acute ischemic stroke admitted to Jeju National University Hospital. The inclusion criteria were: 1) aged ≥18 years, 2) admission within seven days of symptom onset, and 3) an initial National Institute of Health Stroke Scale (NIHSS) score >1 for the affected lower limb. Ultrasound scans of the lower limbs and plasma D-dimer assays were performed on days 7-14 and 15-28 after stroke onset.
Of 285 patients admitted during the study period, 52 patients met inclusion criteria (mean age 74.5, male 40.4%, median initial NIHSS score 12, and unable to walk unassisted at discharge 76.9%). During 7-14 days, 23 of 52 patients (44.2%) had a D-dimer level above 1.57 mg/L, and 9.6% had a level above 5.50 mg/L. Proximal deep vein thrombosis (DVT) was detected in 3 patients (5.8%, 95% confidence Interval 1.2-16.0%) on ultrasound examination. All DVTs were found in elderly female patients with severe leg weakness. No patient was diagnosed with pulmonary embolism during the study period.
The incidence of VTE seems to be very low among Korean patients with acute ischemic stroke. Advanced age, female sex, and severe leg weakness were important risk factors for developing DVT in this study.
Studies have shown that, without prophylaxis approximately 33-50% of Caucasian acutely immobilized stroke patients developed deep vein thrombosis (DVT) within two weeks after the onset of stroke [
Interestingly, previous studies have suggested racial differences in VTE incidence, and Asians were found to have up to 70% lower VTE rates compared to Caucasians [
The D-dimer assay has been used to screen for VTE among various patient populations with a high diagnostic sensitivity, but a limited specificity for VTE at a cutoff level of 0.5 mg/L [
We prospectively and consecutively enrolled patients with acute ischemic stroke admitted to the Department of Neurology of Jeju University Hospital from May 2016 to April 2017. The inclusion criteria were: 1) aged ≥18 years with acute ischemic stroke, 2) hospital admission within seven days of symptom onset, and 3) an initial National Institute of Health Stroke Scale (NIHSS) score >1 for the lower limb affected by the acute ischemic stroke at the time of admission. Patients with significant pre-stroke disability (i.e., a modified Rankin Scale [mRS] score ≥4) or patients with a past history of DVT were excluded. This study was approved by a local ethics committee and written informed consent was obtained from all the patients or their legal representative.
Ultrasound scans of lower limbs were performed during the time periods of 7 to 14 days and 15 to 28 days after stroke onset. The examinations were performed at least 14 days apart. Compression tests were performed on the common femoral vein, femoral vein, and popliteal vein using a Voluson E ultrasound (General Electric Healthcare, Pittsburgh, PA, USA) with a 10-14 MHz linear transducer [
All patients were rated by the Wells score at the time of the ultrasound examination, and it was used to classify the patient’s probability of DVT as low (≤0), moderate (1 or 2), or high (>2) [
Univariate analysis was performed to evaluate the distribution of baseline characteristics of the patients. For bivariate analyses, Chi-square tests, Fisher’s exact test, Student’s
During the recruitment period of 12 months, a total of 285 acute ischemic stroke patients were admitted to the hospital within seven days from onset of stroke symptoms. Of the 285 patients, 52 patients met the eligibility criteria and underwent a first ultrasound examination during the time periods of 7 to 14 days after stroke onset. After the first ultrasound examination, four patients declined participation in the second study, one patient showed a critical condition that precluded the ultrasound examination, and one patient was transferred to another hospital before the second examination. As a result, 46 patients (46/52, 88.5%) received the second ultrasound examination during the time periods of 15 to 28 days (
Agreement between two researchers on the diagnosis of DVT by ultrasound examination was moderate (kappa=0.58). DVT at proximal lower limbs was detected in three patients (5.8%, 95% confidence Interval 1.2-16.0%) on the first ultrasound examination and no new DVTs were found in patients at the second examination. All DVTs were found in elderly female patients, with an NIHSS score of three (i.e., no effort against gravity) for the lower limb affected by the stroke. Although the analyses were limited by the small number of patients with DVT, patients with DVT appeared to have greater stroke severity and more severe leg motor weakness, compared to patients without DVT (
Plasma D-dimer levels were available for all patients at the time of the first ultrasound examination, and in 35 patients (35/46, 76.1%) at the time of the second ultrasound examination. During the time periods of 7 to 14 days, 23 of 52 patients (44.2%) had a D-dimer level above 1.57 mg/L, and 9.6% had levels above 5.50 mg/L. During the time periods of 15 to 28 days, 32.5% of the patients had a D-dimer level above 1.57 mg/L, and 8.7% had levels above 5.50 mg/L (
At the time of the first ultrasound examination, the probability of DVT based on total Wells score of 52 patients was moderate (1-2) in 50 patients (96.2%), and high (>2) in two patients (3.9%), and 11.5% (6/52) of these patients had a score of 2 or more. The probability at the second examination was moderate or high in 91.3% of patients. The Wells score of patients diagnosed with DVT was 3 in one patient and 1 in two patients (
In this study, we found that the incidence of VTE was only 5.8% among Korean patients with ischemic stroke who were immobilized due to leg weakness. The risk seemed to be greatest for elderly female patients with severe lower extremity weakness due to stroke. This study also confirmed that the current reference value of plasma D-dimer was not helpful in screening for VTE among patients with acute ischemic stroke.
Vast variations in VTE prevalence among Asian stroke patients have been reported, depending on the research method [
The exact mechanisms underlying racial differences in VTE rates are not clear. Possible explanations may include variation in the prevalence of genetic and environmental risk factors and accessibility to medical care to provide a correct diagnosis of VTE [
Plasma D-dimer levels are useful for screening DVT in chronic stroke patients receiving rehabilitation [
This study had several limitations. Because this was a single center study with a small number of patients, our findings may not apply to other populations or different clinical settings. In particular, usefulness of the D-dimer assay may be limited in this study due to the small number of patients diagnosed with DVT, as well as the presence of an active cancer patient among the DVT patients. However, we could evaluate the effect of various stroke characteristics on the risk of VTE, including total NIHSS score and severity of leg motor weakness. We could not evaluate the incidence of VTE beyond four weeks after onset of stroke because a substantial number of patients had already been discharged from our institution by that time. Finally, active employment of intermittent pneumatic compression, early rehabilitation therapy, and the use of antiplatelet agents or anticoagulant as part of secondary stroke prevention may have contributed to the low incidence of VTE in the current study.
The incidence of VTE seems to be very low among Korean patients with acute ischemic stroke. Advanced age, female gender, and severe leg weakness due to stroke were important risk factors for developing DVT in this study. Large-scale multicenter research is needed to investigate the exact incidence, biomarkers, and risk factors for VTE in Asian stroke patients to identify high-risk patients and to provide safe and effective VTE prophylaxis.
The online-only supplementary material is available with this article at
Characteristics of the patients by enrollment
Characteristics of the patients by deep vein thrombosis
Flow diagram of study inclusion. GI, gastrointestinal.
Distribution of the plasma D-dimer levels
Baseline characteristics of the patients
Characteristic | Study participants (n=52) |
---|---|
Age (years) | 74.5±12.4 |
Sex (male) | 21 (40.4) |
TOAST classification | |
Large artery atherosclerosis | 17 (32.7) |
Cardiac embolism | 8 (15.4) |
Small vessel occlusion | 18 (34.6) |
Undetermined or other determined etiology | 9 (17.3) |
Initial NIHSS score | 12.2 (7-16.5) |
Mild (0-4) | 6 (11.5) |
Moderate (5-14) | 28 (53.8) |
Severe (≥15) | 18 (34.6) |
NIHSS score of affected lower | |
limb | |
1 | 16 (30.8) |
2 | 17 (32.7) |
3 | 19 (36.5) |
Treatment | |
Intravenous thrombolysis | 5 (9.6) |
Antiplatelet | 37 (71.1) |
Aspirin | 35 (67.3) |
Clopidogrel | 21 (40.4) |
Anticoagulation | 13 (25.0) |
Warfarin | 4 (7.7) |
NOAC | 5 (9.6) |
Early rehabilitation | 47 (90.4) |
Elastic stocking | 3 (5.8) |
Intermittent pneumonic compression | 12 (23.1) |
Plasma D-dimer level (mg/L) | 1.64 (0.8-3.9) |
TOAST, the trial of ORG 10172 in acute stroke treatment; NIHSS, National Institutes of Health Stroke Scale; NOAC, non-vitamin K antagonist oral anticoagulants.
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
Characteristics of three patients with DVT
No. | Patient 1 | Patient 2 | Patient 3 |
---|---|---|---|
Sex/age | F/81 | F/75 | F/95 |
Initial NIHSS score | 7 | 26 | 28 |
Leg motor scale (Rt/Lt) | 3/0 | 3/1 | 3/3 |
Infarct location | Lt. ACA | Lt. MCA | Rt. MCA/ACA |
TOAST classification | LAA | ODE | CE |
Antithrombotics | Aspirin+clopidogrel | Warfarin | Apixaban |
Wells score | 1 | 3 | 1 |
DVT location | Rt. FV | Rt. CFV | Rt. CFV |
D-dimer level (mg/L) | 2.0 | 35.0 | 3.6 |
Discharge mRS | 4 | 5 | 5 |
Cancer history | No | Yes | No |
Intravenous thrombolysis | No | No | No |
Laboratory parameter | |||
WBC (×103/uL) | 6.0 | 6.8 | 10.5 |
Hemglobin (g/dL) | 12.5 | 8.5 | 14.6 |
Platelet (×103/uL) | 259 | 111 | 209 |
PT INR | 0.91 | 1.34 | 1.05 |
PT (sec) | 10.2 | 15.2 | 11.8 |
aPTT (sec) | Not done | 31 | 29 |
DVT, deep vein thrombosis; F, female; NIHSS, National Institutes of Health Stroke Scale; Rt, right; Lt, left; ACA, anterior cerebral artery, MCA, middle cerebral artery; TOAST, the trial of ORG 10172 in acute stroke treatment; LAA, large artery atherosclerosis; ODE, other determined etiology; CE, cardiac embolism; FV, femoral vein; CFV, common femoral vein; mRS, modified Rankin Scale; WBC, white blood cells; PT INR, prothrombin time international normalized ratio; PT, prothrombin time; aPTT, activated partial thromboplastin time.